Process for surface modification of inorganic biomaterial

ABSTRACT

According to the present process for modifying the surface of a biomaterial, there can be precipitated on the surface of a biomaterial a calcium phosphate crystal which is necessary for the biomaterial to form a chemical bonding with human bones. Therefore, the bioactivity of a biomaterial for use as an artifical bone or a dental implant can be improved by the present process.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to a process for modifying the surface of an inorganic biomaterial and more particularly to a process for modifying the surface of an inorganic biomaterial which is useful as an implant material for artificial bones, dental implants, etc., to further improve the bioactivity of the biomaterial.

2. Description of Prior Art

As so-called bioactive ceramics capable of forming a chemical bonding with bones, there are known sintered apatite and a crystallized glass in the system of Na₂ O-K₂ O-MgO-CaO-SiO₂ -P₂ O₅. As the bioactive ceramic, there is further known a crystallized glass in the system of MgO-CaO-P₂ O₅ -SiO₂. This crystallized glass contains an apatite crystal and a wollastonite crystal, and the apatite crystal contributes to the bioactivity and the wollastonite crystal contributes to the mechanical strength. As to the bending strengths of these ceramics, the sintered apatite has about 1,000 to 1,400 kg/cm² ; the Na₂ O-K₂ O-MgO-CaO-SiO₂ -P₂ O₅ system crystallized glass about 1,000 to 1,500 kg/cm² ; the MgO-CaO-P₂ O₅ -SiO₂ system crystallized glass about 1,200 to 1,400 kg/cm².

A CaO-P₂ O₅ -SiO₂ system or CaO-P₂ O₅ -SiO₂ -(MgO, Y₂ O₃) system crystallized glass containing a larger amount of a wollastonite crystal is also known, and it has a high bending strength of 1,700 to 2,300 kg/cm².

However, these bending strengths are not yet fully satisfactory from the standpoint that the above materials are used as an artificial bone or a dental implant. Hence, a biomaterial of higher strength is desired.

As biomaterials of higher strength, there are known composite sintered products consisting of a bioactive crystallized glass as mentioned above and a high strength ceramic powder (e.g. zirconia, alumina, or zirconia-alumina). These composites have a high bending strength of 2,500-3,800 kg/cm² which is comparable to that of sintered alumina.

The above ceramic-crystallized glass composites, however, have lower bioactivity to bones than crystallized glasses per se because in the composites the content of the crystallized glass capable of forming a chemical bonding with bones is reduced by the incorporation of the ceramic incapable of forming a chemical bonding with bones by itself. Therefore, it is desired to improve the bioactivity of the composites.

Crystallized glasses per se have poor bioactivity in some cases, depending upon their compositions. Therefore, it is also desired to improve the bioactivity of crystallized glasses having low bioactivity.

Hence, an object of the present invention is to improve a process for modifying the surface of an inorganic biomaterial such as a crystallized glass or a ceramic-crystallized glass composite in order to improve its bioactivity.

Other objects of the present invention will be apparent from the following descriptions and drawings.

SUMMARY OF THE INVENTION

The present invention has been completed in order to achieve the above objects and provides a process for modifying the surface of an inorganic biomaterial, which comprises treating an inorganic biomaterial containing at least CaO and P₂ O₅ with an aqueous solution containing calcium ion and/or phosphate ion to precipitate a calcium phosphate crystal on the surface of the biomaterial.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the X-ray diffraction patterns of a crystallized glass before and after surface treatment.

FIG. 2 shows the X-ray diffraction patterns of a ceramic-crystallized glass composite before and after surface treatment.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is explained in detail below.

In the process of the present invention, the aqueous solution containing calcium ion and/or phosphate ion, used for the surface treatment of an inorganic biomaterial containing at least CaO and P₂ O₅ is obtained by dissolving in water a water-soluble calcium salt [e.g. CaCO₃, CaO, CaCl₂, CaF₂, Ca(NO₃)₂, Ca(COO)₂, Ca(CH₃ COO)₂, Ca[CH₃ CH(OH)COO]₂ ] and/or a phosphoric acid salt [e.g. H₃ PO₄, (NH₄)₂ HPO₄, NH₄ H₂ PO₄, (NH₄)₃ PO₄, KH₂ PO₄, K₂ HPO₄, Na₂ HPO₄, NaH₂ PO₄ ].

When an inorganic biomaterial containing at least CaO and P₂ O₅ is immersed in the above aqueous solution containing calcium ion and/or phosphate ion, at least either of the CaO and the P₂ O₅ at the surface of the biomaterial dissolves in the aqueous solution in the form of calcium ion or phosphate ion and reacts with the phosphate ion or the calcium ion in the aqueous solution, whereby a calcium phosphate crystal is precipitated on the surface of the inorganic biomaterial. The size and the amount of the crystal precipitated varies depending upon the temperature and time of the above treatment. The calcium phosphate crystal formed on the inorganic biomaterial is fine at a treatment temperature of 10°-50° C. At a treatment temperature of 50°-100° C., the crystal is slightly larger but the treatment time can be relatively short. When the treatment temperature is over 100° C., the aqueous solution boils, making the treatment of the inorganic biomaterial difficult; however, it is still possible to form a calcium phosphate crystal. When the treatment temperature exceeds 200° C., the dissolution rate of the calcium ion and the phosphate ion from the inorganic biomaterial is too high, making it difficult to obtain a calcium phosphate crystal on the surface of the inorganic biomaterial. Accordingly, the treatment temperature is preferably 10°-200° C.

While the treatment time differs by the type of the inorganic material, a short treatment time makes small the amount of the calcium phosphate crystal precipitated and too long a treatment time makes the crystal coarse. In order to obtain a calcium phosphate crystal of appropriate size (0.1-5 μm), a treatment time of about 1-240 hours is preferred although the time differs by the treatment temperature employed.

The type of the calcium phosphate crystal obtained differs by the pH of the aqueous solution used. Brushite (CaHPO₄.2H₂ O) is formed from an aqueous solution having a pH of less than 4; at least one crystal of brushite, octacalcium phosphate [Ca₈ H₂ (PO₄)₆.5H₂ O] and hydroxyapatite [Ca₁₀ (PO₄)₆ (OH)₂ ] is precipitated from an aqueous solution of pH 4-5; and hydroxyapatite is formed from an aqueous solution having a pH of more than 5. When a large amount of carbonic acid is present in the aqueous solution, the hydroxyapatite crystal obtained contains the carbonate ion in some cases. It is preferable that biomaterials have hydroxyapatite on the surfaces because the hydroxyapatite composition is substantially same as the inorganic components of bones. Therefore, the use of an aqueous solution having a pH higher than 5 is preferable. The pH of the aqueous solution can be adjusted using an aqueous solution of an acid or alkali such as HCl, NaOH, NH₄ OH, Ca(OH)₂ or the like.

The treatment temperature and time are determined by subjecting the surface of the inorganic biomaterial during treatment to X-ray diffractometry, infrared reflection spectrum measurement, Raman spectrum measurement and observation by scanning electron microscope.

The reason for formation of a calcium phosphate crystal on the surface of the inorganic biomaterial is that the inorganic biomaterial contains at least CaO and P₂ O₅ and that at least either of them dissolves in the aqueous solution in the form of calcium ion and/or phosphate ion and reacts with the phosphate ion and/or calcium ion in the aqueous solution. The bioactive crystallized glass or the ceramic-bioactive crystallized glass composite can suitably be subjected to surface modification according to the process of the present invention because the CaO and P₂ O₅ contained in the crystallized glass or the composite is soluble in an aqueous solution containing calcium ion and/or phosphate ion.

In the present process, the crystallized glass used as an inorganic biomaterial is preferably a bioactive crystallized glass comprising the following components of the following proportions

    ______________________________________                                         CaO               12-56% by weight                                             P.sub.2 O.sub.5   1-27% by weight                                              SiO.sub.2         22-50% by weight                                             MgO               0-34% by weight                                              Al.sub.2 O.sub.3  0-25% by weight                                              ______________________________________                                    

in a total amount of at least 90% by weight. This crystallized glass contains an apatite crystal, at least one alkaline earth metal silicate crystal selected from wollastonite, diopside, forsterite, akermanite, anorthite, etc., and further in some cases, a β-tricalcium phosphate crystal [β-Ca₃ (PO₄)₂ ].

Also in the present process, the ceramic-crystallized glass composite used as an inorganic biomaterial is preferably a ceramic-bioactive crystallized glass composite obtained by dispersing a reinforcing ceramic selected from zirconia, alumina and a zirconia-alumina ceramic in the above crystallized glass in an amount of 5-50% by volume based on the resulting composite.

The bioactive crystallized glass, or the bioactive crystallized glass used as a matrix in the ceramic-bioactive crystallized glass composite has a compositional restriction as mentioned above. The reason is described below.

When the CaO content is less than 12%, the glass powder has very poor sinterability, making it impossible to obtain a crystallized glass of high strength. When the content is more than 56%, the resulting glass has a high tendency of devitrification. Accordingly, the CaO content is restricted to fall within a range of 12 to 56%, preferably 23 to 50%. When the P₂ O₅ content is less than 1%, the resulting glass has a high tendency of devitrification. When the content is more than 27%, the total amount of the precipitated crystals of alkaline earth metal silicates such as wollastonite, diopside, forsterite, akermanite, anorthite and the like is small. Therefore, the P₂ O₅ content is restricted to 1 to 27%, preferably 1 to 22%. When the SiO₂ content is less than 22%, the glass powder has poor sinterability and the total amount of the precipitated crystals of alkaline earth metal silicates is small. When the content is more than 50%, the resulting glass tends to be devitrified. Hence, the SiO₂ content is restricted to 22 to 50%, preferably 25 to 50%. MgO is not an essential component but when it is contained, an apatite crystal is formed in too small an amount, if the content is more than 34%. Therefore, the MgO content is restricted to 34% or below, preferably 15% or below. Al₂ O₃ is not an essential component, either. However, when it is contained, an apatite crystal is formed in too small an amount, if the content is more than 25%. Therefore, the Al₂ O₃ content is restricted to 25% or below, preferably 17% or below.

The bioactive crystallized glass can compirse, in addition to the above five components, at least one component selected from K₂ O, Li₂ O, Na₂ O, TiO₂, ZrO₂, SrO, Nb₂ O₅, Ta₂ O₅, B₂ O₃, F₂ and Y₂ O₃ (all of which give no harm to human bodies) in a total amount of 10% or less. When the total content of these optional components is more than 10%, the amounts of apatite crystal and alkaline earth metal silicate crystal(s) formed decrease in some cases. Therefore, the content of the above optional components is preferably 10% or less. When the F₂ content is more than 5%, the resulting glass is easily devitrified. When the Y₂ O₃ content is more than 5%, the amounts of apatite crystal and alkaline earth metal silicate crystal(s) formed decrease. Accordingly, the F₂ content and the Y₂ O₃ content are each restricted to 5% or below.

A glass powder having the above composition is sintered and crystallized, whereby a bioactive crystallized glass for use in the present process is obtained. Also, a glass powder having the above composition is mixed with 5-50% by volume, based on the resulting mixture, of a reinforcing ceramic of powder or fiber form, such as zirconia, alumina, zirconia-alumina ceramic or the like, and the mixture is sintered and crystallized, whereby a ceramic-bioactive crystallized glass composite for use in the present process is obtained. The reason for restricting the proportion of the reinforcing ceramic to 5-50% by volume is that when the proportion is less than 5% by volume, the resulting composite has substantially no improvement in mechanical strength over the matrix glass and, when the proportion is more than 50% by volume, the resulting composite has poor densification and has substantially no improvement in mechanical strength over the matrix glass. When the proportion is 5-50% by volume, no such problems exist.

When these inorganic biomaterials containing CaO and P₂ O₅ are immersed in an aqueous solution, tne CaO and P₂ O₅ slightly dissolve therein. Therefore, it is possible to precipitate a calcium phosphate crystal on the surfaces of these inorganic biomaterials according to the present process. Depending upon the treating conditions (treatment time and treatment temperature) employed, it is possible to cover the ceramic portion of the surfaces of the ceramic-crystallized glass composite completely with the calcium phosphate crystal precipitated.

The present invention is explained in more detail below by referring to Examples.

Example 1 (Corresponds to Nos. 1 to 32 of Table 1. )

A material batch for a glass having a composition as shown in Table 1 was prepared from an oxide, a carbonate, a phosphate, a hydrate, a fluoride, etc. The material batch was placed in a platinum crucible and melted at 1,450°-1,500° C. for 2 hours. The resulting melt was poured into water and, after drying, ground to particle sizes of 20 μm or less in a ball mill. The thus obtained glass powder was press-molded at a pressure of 1,000 kg/cm². The resulting molding was heated from room temperature to 1,150° C. at a rate of 3° C./min and kept at 1,150° C. for 2 hours in an electric furnace to give rise to sintering and crystallization. Then the molding was cooled to room temperature in the furnace to obtain a crystallized glass.

A test piece of 15 mm×20 mm×2 mm was prepared by cutting the above crystallized glass and then polished at the surface with a No. 1,000 alumina powder. The test piece was then surface-treated under conditions as shown in Table 1. The surface of the thus treated test piece was observed by a scanning electron microscope, which showed the formation of a product on the entire surface of the test piece. This product was confirmed by the X-ray diffraction and Raman spectrum to be a calcium phosphate crystal as shown in Table 1. This matter is explained on the case of No. 2 of Table 1. FIG. 1 shows the X-ray diffraction patterns before and after surface treatment, of the No. 2 material of Table 1. According to FIG. 1, when the crystallized glass having an apatite crystal and a diopside crystal as crystaline phases was treated according to the present process, the diopside peak became too small to confirm the presence of diopside, and the apatite peak became very large. This indicates that the entire surface of the crystallized glass was covered with apatite.

                                      TABLE 1                                      __________________________________________________________________________                        Material No.                                                                   1           2         3           4                         __________________________________________________________________________     Crystallized glass used for treatment                                          Glass composition (wt. %)                                                      CaO                44.7        36.3      26.8        24.6                      P.sub.2 O.sub.5    16.3        16.3      14.1        16.0                      SiO.sub.2          34.2        35.4      34.1        28.7                      Others             MgO 4.6     MgO 11.5  MgO 11.5    MgO 30.7                                     F.sub.2 0.2 F.sub.2 0.5                                                                              Al.sub.2 O.sub.3 12.7                                                          F.sub.2 0.8                           Crystalline phases precipitated                                                                   Apatite     Apatite   Apatite     Apatite                   in the crystallized glass                                                                         Wollastonite                                                                               Diopside  Anorthite   Forsterite                                   Diopside              Diopside    Diopside                                                           Forsterite  β-Tricalcium                                                  β-Tricalcium                                                                          phosphate                                                          phosphate                             Treatment conditions                                                           Source of calcium ion and/or                                                                      H.sub.3 PO.sub.4                                                                           H.sub.3 PO.sub.4                                                                         CaCO.sub.3  Ca(CH.sub.3 COO).sub.                                                          2 +                       phosphate ion                                        H.sub.3 PO.sub.4          Concentration in solution (%)                                                                     5           5         5           5 (total)                 PH                 7.2         8.7       4.5         7.5                       Reagent used for pH adjustment                                                                    Ca(OH).sub.2                                                                               NaOH      HCl         NH.sub.4 OH               Treatment temperature (°C.)                                                                37          37        80          80                        Treatment time (hour)                                                                             120         240       48          48                        Product formed on surface                                                                         Hydroxyapatite                                                                             Hydroxyapatite                                                                           Brushite    Hydroxyapatite                                                     Octacalcium                                                                    phosphate                                                                      Hydroxyapatite                        __________________________________________________________________________                        5           6         7           8                         __________________________________________________________________________     Crystallized glass used for treatment                                          Glass composition (wt. %)                                                      CaO                26.1        16.6      47.4        47.4                      P.sub.2 O.sub.5    23.0        16.2      6.2         6.2                       SiO.sub.2          29.8        37.2      42.2        42.2                      Others             MgO 18.6    MgO 29.5  Y.sub.2 O.sub.3                                                                            MgO 2.0                                      F.sub.2 0.5 F.sub.2 0.5                                                                              ZrO.sub.2 2.0                                                                              Ta.sub.2 O.sub.5                                                               2.0                                          Li.sub.2 O 2.0        F.sub.2 0.2 F.sub.2 0.2               Crystalline phases precipitated                                                                   Apatite     Apatite   Apatite     Apatite                   in the crystallized glass                                                                         Akermanite  Diopside  Wollastonite                                                                               Wollastonite                                 Diopside    Forsterite                                                         β-Tricalcium                                                              phosphate                                                   Treatment conditions                                                           Source of calcium ion and/or                                                                      Ca(COO).sub.2                                                                              CaO + CaF.sub.2 +                                                                        H.sub.3 PO.sub.4                                                                           H.sub.3 PO.sub.4          phosphate ion                  CaCl.sub.2                                      Concentration in solution (%)                                                                     5           5 (total) 20          20                        PH                 3.8         4.2       7.4         7.4                       Reagent used for pH adjustment                                                                    HCl         HCl       NH.sub.4 OH NH.sub.4 OH               Treatment temperature (°C.)                                                                80          80        95          95                        Treatment time (hour)                                                                             48          48        48          48                        Product formed on surface                                                                         Brushite    Brushite  Hydroxyapatite                                                                             Hydroxyapatite                                           Octacalcium                                                                    phosphate                                       __________________________________________________________________________                        9           10        11          12                        __________________________________________________________________________     Crystallized glass used for treatment                                          composition (wt. %)                                                            CaO                48.3        47.9      48.3        48.3                      P.sub.2 O.sub.5    6.3         6.3       6.3         6.3                       SiO.sub.2          43.2        42.6      43.2        43.2                      Others             F.sub.2 0.2 F.sub.2 0.2                                                                              F.sub.2 0.2 F.sub.2 0.2                                  TiO.sub.2 2.0                                                                              K.sub.2 O 3.0                                                                            SrO 2.0     Nb.sub.2 O.sub.5                                                               2.0                       Crystalline phases precipitated                                                                   Apatite     Apatite   Apatite     Apatite                   in the crystallized glass                                                                         Wollastonite                                                                               Wollastonite                                                                             Wollastonite                                                                               Wollastonite              Treatment conditions                                                           Source of calcium ion and/or                                                                      H.sub.3 PO.sub.4                                                                           CaCl.sub.2 + KH.sub.2 PO.sub.4                                                           H.sub.3 PO.sub.4                      phosphate ion                                                                  Concentration in solution (%)                                                                     20          10 (total)                                                                               20          20                        PH                 7.4         7.0       7.2         7.2                       Reagent used for pH adjustment                                                                    NH.sub.4 OH NH.sub.4 OH                                                                              NH.sub.4 OH NH.sub.4 OH               Treatment temperature (°C.)                                                                95          95        95          95                        Treatment time (hour)                                                                             48          48        48          48                        Product formed on surface                                                                         Hydroxyapatite                                                                             Hydroxyapatite                                                                           Hydroxyapatite                                                                             Hydroxyapatite            __________________________________________________________________________                        13          14        15          16                        __________________________________________________________________________     Crystallized glass used for treatment                                          Glass composition (wt. %)                                                      CaO                48.3        48.3      23.2        49.2                      P.sub.2 O.sub.5    6.3         6.3       27.0        1.0                       SiO.sub. 2         43.2        43.2      49.8        49.8                      Others             F.sub.2 0.2 F.sub.2 0.2                                                        Na.sub.2 O 2.0                                                                             B.sub.2 O.sub.3 2.0                             Crystalline phases precipitated                                                                   Apatite     Apatite   Apatite     Apatite                   in the crystallized glass                                                                         Wollastonite                                                                               Wollastonite                                                                             Wollastonite                                                                               Wollastonite                                                       β-Tricalcium                                                              phosphate                             Treatment conditions                                                           Source of calcium ion and/or                                                                      Ca(NO.sub.3).sub.2 + H.sub.3 PO.sub.4                                                      H.sub.3 PO.sub.4                                                                         Ca[CH.sub.3 CH(OH)COO].sub.2                                                               (NH.sub.4).sub.2                                                               HPO.sub.4                 phospate ion                                                                   Concentration in solution (%)                                                                     10 (total)  20        20          20                        PH                 8.0         7.8       8.2         8.0                       Reagent used for pH adjustment                                                                    NH.sub.4 OH NH.sub.4 OH                                                                              NaOH        Not used                  Treatment temperature (°C.                                                                 95          95        95          120                       Treatment time (hour)                                                                             48          48        48          24                        Product formed on surface                                                                         Hydroxyapatite                                                                             Hydroxyapatite                                                                           Hydroxyapatite                                                                             Hydroxyapatite            __________________________________________________________________________                        17          18        19          20                        __________________________________________________________________________     Crystallized glass used for treatment                                          Glass composition (wt. %)                                                      CaO                47.5        55.6      49.3        47.8                      P.sub.2 O.sub.5    14.0        22.0      6.5         6.5                       SiO.sub.2          38.5        22.4      44.0        44.0                      Others                                   F.sub.2 0.2 MgO 1.5                                                                        F.sub.2 0.5               Crystalline phases precipitated                                                                   Apatite     Apatite   Apatite     Apatite                   in the crystallized glass                                                                         Wollastonite                                                                               Wollastonite                                                                             Wollastonite                                                                               Wollastonite              Treatment conditions                                                           Source of calcium ion and/or                                                                      (NH.sub.4).sub.2 HPO.sub.4                                                                 (NH.sub.4).sub.2 HPO.sub.4                                                               (NH.sub.4).sub.2 HPO.sub.4                                                                 (NH.sub.4).sub.2                                                               HPO.sub.4                 phosphate ion                                                                  Concentration in solution (%)                                                                     20          20        20          5                         PH                 7.4         7.4       7.4         7.3                       Reagent used for pH adjustment                                                                    Not used    Not used  Not used    Not used                  Treatment temperature (°C.)                                                                120         120       200         50                        Treatment time (hour)                                                                             24          24        1           120                       Product formed on surface                                                                         Hydroxyapatite                                                                             Hydroxyapatite                                                                           Hydroxyapaptite                                                                            Hydroxyapatite            __________________________________________________________________________                        21          22        23          24                        __________________________________________________________________________     Crystallized glass used for treatment                                          Glass composition (wt. %)                                                      CaO                12.0        45.0      45.0        45.0                      P.sub.2 O.sub.5    15.5        6.0       6.0         6.0                       SiO.sub.2          47.7        39.0      39.0        39.0                      Others             Al.sub.2 O.sub.3 24.8                                                                      K.sub.2 O 9.5                                                                            Li.sub.2 O 9.5                                                                             Na.sub.2 O 9.5            Crystalline phases precipitated                                                                   Apatite     Apatite   Apatite     Apatite                   in the crystallized glass                                                                         Anorthite   Wollastonite                                                                             Wollastonite                                                                               Wollastonite                                 β-Tricalcium                                                                          β-Tricalcium                                                                        β-Tricalcium                                                                          β-Tricalcium                            phosphate   phosphate phosphate   phosphate                 Treatment conditions                                                           Source of calcium ion and/or                                                                      Ca(NO.sub.3).sub.2 + NaH.sub.2 PO.sub.4                                                    K.sub.2 HPO.sub.4                                                                        (NH.sub.4).sub.2 HPO.sub.4                                                                 Na.sub.2 HPO.sub.4        phosphate ion                                                                  Concentation in solution (%)                                                                      5 (total)   5         5           5                         PH                 8.2         8.0       7.6         7.5                       Reagent used for pH adjustment                                                                    Not used    Not used  Not used    Not used                  Treatment temperature (°C.)                                                                100         100       95          95                        Treatment time (hour)                                                                             48          48        48          48                        Product formed on surface                                                                         Hydroxyapatite                                                                             Hydroxyapatite                                                                           Hydroxyapatite                                                                             Hydroxyapatite            __________________________________________________________________________                        25          26        27          28                        __________________________________________________________________________     Crystallized glass used for treatment                                          Glass composition (wt. %)                                                      CaO                45.0        45.0      45.0        45.0                      P.sub.2 O.sub.5    6.0         6.0       6.0         6.0                       SiO.sub.2          39.0        39.0      39.0        39.0                      Others             TiO.sub.2 9.5                                                                              ZrO.sub.2 9.5                                                                            SrO 9.5     Nb.sub.2 O.sub.5                                                               9.5                                          F.sub.2 0.5 F.sub.2 0.5                                                                              F.sub.2 0.5 F.sub.2 0.5               Crystalline phases precipitated                                                                   Apatite     Apatite   Apatite     Apatite                   in the crystallized glass                                                                         Wollastonite                                                                               Wollastonite                                                                             Wollastonite                                                                               Wollastonite                                 β-Tricalcium                                                                          β-Tricalcium                                                                        β-Tricalcium                                                                          β-Tricalcium                            phosphate   phosphate phosphate   phosphate                 Treatment conditions                                                           Source of calcium ion and/or                                                                      (NH.sub.4).sub.2 HPO.sub.4                                                                 (NH.sub.4).sub.2 HPO.sub.4                                                               (NH.sub.4).sub.2 HPO.sub.4                                                                 (NH.sub.4).sub.2                                                               HPO.sub.4                 phospate ion                                                                   Concentration in solution (%)                                                                     5           5         5           5                         PH                 7.5         7.5       7.2         7.5                       Reagent used for pH adjustment                                                                    Not used    Not used  Not used    Not used                  Treatment temperature (°C.)                                                                95          95        95          95                        Treatment time (hour)                                                                             48          48        48          48                        Product formed on surface                                                                         Hydroxyapatite                                                                             Hydroxyapatite                                                                           Hydroxyapatite                                                                             Hydroxyapatite            __________________________________________________________________________                        29          30        31          32                        __________________________________________________________________________     Crystallized glass used for treatment                                          Glass composition (wt. %)                                                      CaO                45.0        45.0      45.0        45.0                      P.sub.2 O.sub.5    6.0         6.0       6.0         6.0                       SiO.sub.2          39.0        39.0      44.5        44.0                      Others             Ta.sub.2 O.sub.5 9.5                                                                       B.sub.2 O.sub.3 9.5                                                                      F.sub.2 4.5 Y.sub.2 O.sub.3 5.0                          F.sub.2 0.5 F.sub.2 0.5                                     Crystalline phases precipitated                                                                   Apatite     Apatite   Apatite     Apatite                   in the crystallized glass                                                                         Wollastonite                                                                               Wollastonite                                                                             Wollastonite                                                                               Wollastonite                                 β-Tricalcium                                                                          β-Tricalcium                                                                        β-Tricalcium                                                                          β-Tricalcium                            phosphate   phosphate phosphate   phosphate                 Treatment conditions                                                           Source of calcium ion and/or                                                                      (NH.sub.4).sub.2 HPO.sub.4                                                                 (NH.sub.4).sub.2 HPO.sub.4                                                               NH.sub.4 H.sub.2 PO.sub.4                                                                  (NH.sub.4).sub.3                                                               PO.sub.4                  phoshpate ion                                                                  Concentration in solution (%)                                                                     5           5         5           5                         PH                 7.4         7.4       7.4         7.6                       Reagent used for pH adjustment                                                                    Not used    Not used  Not used    Not used                  Treatment temperature (°C.)                                                                95          95        95          95                        Treatment time (hour)                                                                             48          48        48          48                        Product formed on surface                                                                         Hydroxyapatite                                                                             Hydroxyapatite                                                                           Hydroxyapatite                                                                             Hydroxyapatite            __________________________________________________________________________

Example 2 (Corresponds to Nos. 1 to 21 of Table 2).

A material batch for a glass having a composition as shown in Table 2 was prepared from an oxide, a carbonate, a phosphate, a hydrate, a fluoride, etc. The material batch was placed in a platinum crucible and melted at 1,450°-1,550° C. for 2 hours. The resulting melt was poured into water and, after drying, ground to particle size of 20 μm or less in a ball mill. The obtained glass powder was mixed with a zirconia powder, a zirconia fiber, an alumina powder, an alumina fiber (all of these were commercially available), or a zirconai-alumina ceramic powder (which was obtained by calcinating a mixture of a tetragonal zirconia powder and an α-alumina powder) in proportions as shown in Table 2. The mixture was wet-blended for several hours in a ball mill and dried. The dried mixture placed in a graphite mold was heated from room temperature to 1,150° C. at a constant rate of 3° C./min in a furnace while applying a pressure of 300 kg/cm² and kept at 1,150° C. for 2 hours to give rise to sintering and crystallization. Then, the resulting molding was cooled to room temperature in the furnace to obtain a ceramic-crystallized glass composite.

A test piece of 15 mm×20 mm×2 mm was prepared by cutting the above ceramic-crystallized glass composite and then polished at the surface with a No. 1,000 alumina powder. The test piece was then surface-treated under conditions as shown in Table 2. The surface of the thus treated test piece was observed by a scanning electron microscope. The observation showed that a product was formed not only on the surface of the matrix glass (the crystallized glass) but also on the surface of the ceramic and that the entire surface of the ceramic-crystallized glass composite was covered with the product. The product was confirmed by the X-ray diffraction pattern and Raman spectrum to be a calcium phosphate crystal as shown in Table 2. This matter is explained on the case of No. 9 of Table 2. FIG. 2 shows the X-ray diffraction patterns before and after treatment, of the No. 9 mateiral of Table 2. According to FIG. 2, when the ceramic-crystallized glass composite obtained by dispersing a zirconia-alumina powder as a reinforcing ceramic in a crystallized glass having an apatite crystal and a wollastonite crystal as crystalline phases was treated according to the present process, the peaks of wollastonite, zirconia and alumina became small and the peak of apatite became large. This indicates that apatite was precipitated on the entire surface of the ceramic-crstallized glass composite.

With respect to the bending strengths before and after surface treatment, the No. 2 material showed 3,000 kg/cm² before treatment and 3,200 kg/cm² after treatment; the No. 3 showed 3,000 kg/cm² before treatment and 3,000 kg/cm² after treatment; the No. 7 material showed 3,300 kg/cm² before treatment and 3,100 kg/cm₂ after treatment; the No. 9 material showed 3,800 kg/cm² before treatment and 3,800 kg/cm² after treatment; and the No. 10 material showed 3,100 kg/cm² before treatment and 3,000 kg/cm² after treatment. Thus, any of these materials showed no significant reduction in bending strength by treatment, while some material showed slight increase in bending strength by treatment. Similarly, any of other materials of Table 2 showed no significant reduction in bending strength by treatment.

                                      TABLE 2                                      __________________________________________________________________________                      Material No.                                                  __________________________________________________________________________                      1            2           3           4                        __________________________________________________________________________     Ceramic-crystallized glass                                                     composite used for treatment                                                   Crystallized glass as a matrix                                                 Composition (wt %)                                                             CaO              12.0         47.8        36.3        40.0                     P.sub.2 O.sub.5  15.5         6.5         16.3        15.5                     SiO.sub.2        47.7         44.0        35.4        28.0                     Others           Al.sub.2 O.sub.3 24.8                                                                       MgO 1.5     MgO 11.5    MgO 12.0                                               F.sub.2 0.2 F.sub.2 0.5 F.sub.2 0.5                                                                    ZrO.sub.2 4.0            Crystalline phases precipitated                                                                 Apatite      Apatite     Apatite     Apatite                  in the crystallized glass                                                                       Anorthite    Wollastonite                                                                               Diopside    Diopside                                  β-Tricalcium                    Akermanite                                phosphate                            Forsterite               Reforcing ceramic                                                              Type of ceramic  Zirconia powder                                                                             Zirconia powder                                                                            Zirconia powder                                                                            Zirconia powder          Amount used (vol. % in composite)                                                               20           20          20          20                       Treatment conditions                                                           Source of calcium ion and/or                                                                    Ca(NO.sub.3).sub.2 + H.sub.3 PO.sub.4                                                       (NH.sub.4).sub.2 HPO.sub.4                                                                 (NH.sub.4).sub.2 HPO.sub.4                                                                 (NH.sub.4).sub.2                                                               HPO.sub.4                phosphate ion                                                                  Concentration in solution (%)                                                                   10 (total)   20          20          20                       PH               8.0          8.0         8.0         7.3                      Reagent for pH adjustment                                                                       NH.sub.4 OH  Not used    Not used    Not used                 Treatment temperature (°C.)                                                              90           90          90          90                       Treatment time (hour)                                                                           48           48          48          48                       Product formed on surface                                                                       Hydroxyapatite                                                                              Hydroxyapatite                                                                             Hydroxyapatite                                                                             Hydroxyapatite           __________________________________________________________________________                      5            6           7           8                        __________________________________________________________________________     Ceramic-crystallized glass                                                     composite used for treatment                                                   Crystallized glass as a matrix                                                 Composition (wt. %)                                                            CaO              24.6         47.8        47.8        47.8                     P.sub.2 O.sub.5  16.0         6.5         6.5         6.5                      SiO.sub.2        28.7         44.0        44.0        44.0                     Others           MgO 30.7     Mgo 1.5     MgO 1.5     MgO 1.5                                                F.sub.2 0.2 F.sub.2 0.2 F.sub.2 0.2              Crystalline phases precipitated                                                                 Apatite      Apatite     Apatite     Apatite                  in the crystallized glass                                                                       Forsterite   Wollastonite                                                                               Wollastonite                                                                               Wollastonite                              Diopside                                                                       β-Tricalcium                                                              phosphate                                                     Reinforcing ceramic                                                            Type of ceramic  Zirconia powder                                                                             Zirconia fiber                                                                             Alumina powder                                                                             Alumina fiber            Amount used (vol. % in composite)                                                               20           20          20          20                       Treatment conditions                                                           Source of calcium ion and/or                                                                    Ca(CH.sub.3 COO).sub.2 + H.sub.3 PO.sub.4                                                   (NH.sub.4).sub.2 HPO.sub.4                                                                 (NH.sub.4).sub.2 HPO.sub.4                                                                 (NH.sub.4).sub.2                                                               HPO.sub.4                phosphate ion                                                                  Concentration in solution (%)                                                                   5 (total)    5           5           5                        PH               7.5          7.3         7.3         7.3                      Reagent for pH adjustment                                                                       NH.sub.4 OH  Not used    Not used    Not used                 Treatment temperature (°C.)                                                              80           95          95          95                       Treatment time (hour)                                                                           48           48          48          48                       Product formed on surface                                                                       Hydroxyapatite                                                                              Hydroxyapatite                                                                             Hydroxyapatite                                                                             Hydroxyapatite           __________________________________________________________________________                      9            10          11          12                       __________________________________________________________________________     Ceramic-crystallized glass                                                     composite used for treatment                                                   Crystallized glass as a matrix                                                 Composition (wt. %)                                                            CaO              47.8         47.8        47.8        47.8                     P.sub.2 O.sub.5  6.5          6.5         6.5         6.5                      SiO.sub.2        44.0         44.0        44.0        44.0                     Others           MgO 1.5      MgO 1.5     MgO 1.5     MgO 1.5                                   F.sub.2 0.2  F.sub.2 0.2 F.sub.2 0.2 F.sub.2 0.2              Crystalline phases precipitated                                                                 Apatite      Apatite     Apatite     Apatite                  in the crystallized glass                                                                       Wollastonite Wollastonite                                                                               Wollastonite                                                                               Wollastonite             Reinforcing ceramic                                                            Type of ceramic  Zirconia-alumina                                                                            Zirconia-alumina                                                                           Zirconia-alumina                                                                           Zirconia powder                           powder (ZrO.sub.2 :Al.sub.2 O.sub.3 =                                                       powder (ZrO.sub.2 :Al.sub.2 O.sub.3                                                        powder (ZrO.sub.2 :Al.sub.2                                                    O.sub.3 =                                             80:20 wt. %) 60:40 wt. %)                                                                               20:80 wt. %)                         Amount used (vol. % in composite)                                                               20           20          20          35                       Treatment conditions                                                           Source of calcium ion and/or                                                                    (NH.sub.4).sub.2 HPO.sub.4                                                                  (NH.sub.4).sub.2 HPO.sub.4                                                                 (NH.sub.4).sub.2 HPO.sub.                                                                  (NH.sub.4).sub.2                                                               HPO.sub.4                phosphate ion                                                                  Concentration in solution (%)                                                                   5            5           5           5                        PH               7.3          7.3         7.3         7.3                      Reagent for pH adjustment                                                                       Not used     Not used    Not used    Not used                 Treatment temperature (°C.)                                                              95           95          95          95                       Treatment time (hour)                                                                           48           48          48          48                       Product formed on surface                                                                       Hydroxyapatite                                                                              Hydroxyapatite                                                                             Hydroxyapatite                                                                             Hydroxyapatite           __________________________________________________________________________                      13           14          15          16                       __________________________________________________________________________     Ceramic-crystallized glass                                                     composite used for treatment                                                   Crystallized glass as a matrix                                                 Composition (wt. %)                                                            CaO              47.8         26.1        16.6        47.8                     P.sub.2 O.sub.5  6.5          23.0        16.2        6.5                      SiO.sub.2        44.0         29.8        37.2        44.0                     Others           MgO 1.5      MgO 18.6    MgO 29.5    MgO 1.5                                   F.sub.2 0.2  F.sub.2 0.5 F.sub.2 0.5 F.sub.2 0.2              Crystalline phases precipitated                                                                 Apatite      Apatite     Apatite     Apatite                  in the crystallized glass                                                                       Wollastonite Akermanite  Diopside    Wollastonite                                           Diopside                                                                       β-Tricalcium                                                              phosphate                                        Reinforcing ceramic                                                            Type of ceramic  Zirconia powder                                                                             Zirconia powder                                                                            Zirconia powder                                                                            Zirconia powder          Amount used (vol. % in composite)                                                               50           20          20          20                       Treatment conditions                                                           Source of calcium ion and/or                                                                    (NH.sub.4).sub.2 HPO.sub.4                                                                  Ca(NO.sub.3).sub.2                                                                         CaCl.sub.2  (NH.sub.4).sub.2                                                               HPO.sub.4                phosphate ion                                                                  Concentration in solution (%)                                                                   5            5           5           5                        PH               7.3          3.7         4.2         7.3                      Reagent for pH adjustment                                                                       Not used     HCl         HCl         Not used                 Treatment temperature (°C.)                                                              95           80          80          37                       Treatment time (hour)                                                                           48           48          48          240                      Product formed on surface                                                                       Hydroxyapatite                                                                              Brushite    Brushite    Hydroxyapatite                                                     Octacalcium phosphate                __________________________________________________________________________                      17           18          19          20                       __________________________________________________________________________     Ceramic-crystallized glass                                                     composite used for treatment                                                   Crystallized glass as a matrix                                                 Composition (wt. %)                                                            CaO              47.8         47.8        47.7        36.3                     P.sub.2 O.sub.5  6.5          6.5         6.5         16.3                     SiO.sub.2        44.0         44.0        44.0        35.4                     Others           MgO 1.5      MgO 1.5     MgO 1.5     MgO 11.5                                  F.sub.2 0.2  F.sub.2 0.2 F.sub.2 0.3 F.sub.2 0.5              Crystalline phases precipitated                                                                 Apatite      Apatite     Apatite     Apatite                  in the crystallized glass                                                                       Wollastonite Wollastonite                                                                               Wollastonite                                                                               Diopside                 Reinforcing ceramic                                                            Type of ceramic  Zirconia powder                                                                             Zirconia powder                                                                            Zirconia powder                                                                            Zirconia powder          Amount used (vol. % in composite)                                                               20           20          5           10                       Treatment conditions                                                           Source of calcium ion and/or                                                                    (NH.sub.4).sub.2 HPO.sub.4                                                                  (NH.sub.4).sub.2 HPO.sub.4                                                                 H.sub.3 PO.sub.4                                                                           H.sub.3 PO.sub.4         phosphate ion                                                                  Concentration in solution (%)                                                                   5            5           5           5                        PH               7.3          7.3         7.5         7.6                      Reagent for pH adjustment                                                                       Not used     Not used    NaOH        NaOH                     Treatment temperature (°C.)                                                              150          200         90          90                       Treatment time (hour)                                                                           5            1           48          48                       Product formed on surface                                                                       Hydroxyapatite                                                                              Hydroxyapatite                                                                             Hydroxyapatite                                                                             Hydroxyapatite           __________________________________________________________________________                                                        21                          __________________________________________________________________________                                       Ceramic-crystallized glass                                                     composite used for treatment                                                   Crystallized glass as a matrix                                                 Composition (wt. %)                                                            CaO              47.7                                                          P.sub.2 O.sub.5  6.5                                                           SiO.sub.2        44.0                                                          Others           MgO 1.5                                                                        F.sub.2 0.3                                                   Crystalline phases precipitated                                                                 Apatite                                                       in the crystallized glass                                                                       Wollastonite                                                  Reinforcing ceramic                                                            Type of ceramic  Zirconia-alumina                                                               powder (ZrO.sub.2                                                              :Al.sub.2 O.sub.3 =                                                            60:40 wt. %)                                                  Amount used (vol. % in                                                                          40mposite)                                                    Treatment conditions                                                           Source of calcium ion                                                                           (NH.sub.4).sub.2                                                               HPO.sub.4                                                     phosphate ion                                                                  Concentration in solution                                                                       5%)                                                           PH               7.3                                                           Reagent for pH adjustment                                                                       Not used                                                      Treatment temperature                                                                           90degree.C.)                                                  Treatment time (hour)                                                                           48                                                            Product formed on surface                                                                       Hydroxyapatite              __________________________________________________________________________

As described in detail above, according to the present process for modifying the surface of a biomaterial, there can be precipitated on the surface of a biomaterial a calcium phosphate crystal which is necessary for the biomaterial to form a chemical bonding with human bones. Therefore, the bioactivity of a biomaterial for use as an artificial bone or a dental implant can be improved by the present process. 

What is claimed is:
 1. A process for modifying the surface of a bioactive ceramic-crystallized-glass-composite biomaterial, which comprises providing said biomaterial, as a biomaterial which contains a crystallized glass of at least 12-56% CaO, 1-27% P₂ O₅ and 22-50% SiO₂ and a reinforcing amount of a reinforcing ceramic of zirconia and/or alumina ceramic dispersed in the crystallized glass, contacting said biomaterial with an aqueous solution containing calcium ion and/or phosphate ion to dissolve CaO and/or P₂ O₅ from said biomaterial into said solution and precipitate a calcium phosphate crystal on the surface of said biomaterial, said contacting being effected for sufficient time and temperature to improve bioactivity of the biomaterial and to completely cover the composite biomaterial with calcium phosphate crystal, and removing said composite biomaterial from the aqueous solution as a calcium-phosphate-covered biomaterial with increased bioactivity.
 2. A process according to claim 1, wherein the composite is a ceramic-bioactive crystallized glass composite obtained by dispersing a reinforcing ceramic selected from zirconia, alumina and zirconia-alumina ceramic in a bioactive crystallized glass comprising the following components of the following proportions

    ______________________________________                                         CaO               12-56% by weight                                             P.sub.2 O.sub.5   1-27% by weight                                              SiO.sub.2         22-50% by weight                                             MgO               0-34% by weight                                              Al.sub.2 O.sub.3  0-25% by weight                                              ______________________________________                                    

in a total content of at least 90% by weight and having an apatite crystal and at least one alkaline earth metal silicate crystal selected from the group consisting of wollastonite, diopside, forsterite, akermanite and anorthite, precipitated therein.
 3. A process according to claim 2, wherein the amount of a reinforcing ceramic dispersed in a bioactive crystallized glass is 5-50% by volume based on the composite.
 4. A process according to claim 1, wherein the aqueous solution has a pH of 5 or more.
 5. A process according to claim 1, wherein the temperature of the aqueous solution is from 10° to 200° C.
 6. A process according to claim 1, wherein the treatment is conducted for 1-240 hours. 